A research group at Nagoya City University Graduate School, Kumamoto University Graduate School, and Kitasato University has revealed that ivermectin, whose inhibitory action against multiple viruses has been attracting attention in recent years, has the effect of suppressing hepatitis B virus (HBV) infection.
HBV infects hepatocytes and causes chronic hepatitis, liver cirrhosis, and liver cancer.Nucleic acid analog preparations are currently mainly used as therapeutic agents for chronic hepatitis caused by HBV infection. It can remove HBV DNA by inhibiting reverse transcriptase of HBV, but cannot negatively neutralize cccDNA (viral DNA essential for HBV virus replication) and HBs antigen (envelope protein that constitutes the outer shell of HBV). Even if the HBV DNA concentration is low, if the HBs antigen concentration is high, the rate of progression to liver lesions and carcinogenesis is considered to be high, so HBs antigen negative conversion is important.
Ivermectin is a treatment for scabies and onchocerciasis.In recent years, it has been reported that it specifically inhibits intracellular nucleo-cytoplasmic transporters (importin α/β) and suppresses the replication of RNA viruses such as human immunodeficiency virus type 1 (HIV-1) and dengue virus. there isThe research group focused on the fact that HBV core protein (HBc), which is a component of HBV, is transported into the nucleus by importin α/β, and investigated the anti-HBV effects of ivermectin.
As a result, ivermectin reduced cccDNA and HBs antigen in both NTCP-forced hepatoma cells (hepatoma cells that can be transiently infected with HBV) and human liver chimeric mouse-derived hepatocytes.Ivermectin also decreased the nuclear abundance of HBc and importin α1 (karyopherin α2, KPNA2), a subtype of importin α.In addition, the production of cccDNA and HBs antigen was suppressed in the state of suppressing KPNA2 expression, suggesting the involvement of KPNA2 in HBV infection.
This study shows the new potential of ivermectin as a therapeutic drug, and is expected to lead to the elucidation of the interaction between HBV and host factors.
Paper information:[Viruses] Ivermectin Inhibits HBV Entry into the Nucleus by Suppressing KPNA2
